Viberzi (eluxadoline)

No dosing information is available for this tab.

Eluxadoline is administered orally with food.

No dosing information is available for this tab.

Metabolism of eluxadoline via the cytochrome P-450 (CYP) enzyme system has not been clearly established, and the potential for eluxadoline to inhibit CYP3A4 in the gut has not been established.

In vitro, eluxadoline is neither an inducer of CYP isoenzymes 1A2, 2C9, 2C19, or 3A4 nor an inhibitor of CYP isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, or 3A4 at clinically relevant systemic concentrations. Although CYP2E1 was slightly inhibited by eluxadoline, clinically meaningful pharmacokinetic interactions are unlikely. However, in vitro studies were not adequate to establish the potential for eluxadoline to inhibit CYP3A4 in the gut.

In vitro studies suggest that eluxadoline is a substrate for organic anion transporter (OAT) 3, organic anion transport protein (OATP) 1B1, bile salt export pump (BSEP), and multidrug resistance protein (MRP) 2, but is not a substrate for organic cation transporter (OCT) 1 or 2, OAT1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Based on in vitro studies, clinically meaningful pharmacokinetic interactions via inhibition of OCT1, OCT2, OAT1, OAT3, OATP1B3, BSEP, and MRP2 by eluxadoline are unlikely. However, in vitro studies were not adequate to establish the potential for eluxadoline to inhibit P-gp in the gut.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Eluxadoline/Anticholinergics; Opioids

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Eluxadoline is a mixed mu-opioid and kappa-opioid agonist and delta-opioid antagonist and may alter or slow down gastrointestinal transit.(1)

CLINICAL EFFECTS: Constipation related adverse events that sometimes required hospitalization have been reported, including the development of intestinal obstruction, intestinal perforation, and fecal impaction.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid use with other drugs that may cause constipation. If concurrent use is necessary, evaluate the patient's bowel function regularly. Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(1) Instruct patients to stop eluxadoline and immediately contact their healthcare provider if they experience severe constipation. Loperamide may be used occasionally for acute management of severe diarrhea, but must be discontinued if constipation develops.(1)

DISCUSSION: In phase 3 clinical trials, constipation was the most commonly reported adverse reaction (8%). Approximately 50% of constipation events occurred within the first 2 weeks of treatment while the majority occurred within the first 3 months of therapy. Rates of severe constipation were less than 1% in patients receiving eluxadoline doses of 75 mg and 100 mg.(1)

Eluxadoline/Oatp1b1 Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: OATP1B1 inhibitors may decrease the hepatic uptake of eluxadoline.(1)

CLINICAL EFFECTS: Concurrent use of OATP1B1 inhibitors may result in elevated levels of and side effects from eluxadoline, including constipation, nausea, abdominal pain, and impaired mental and physical abilities.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving concurrent OATP1B1 inhibitors should receive a dose of eluxadoline of 75 mg twice daily. Monitor patients for impaired mental or physical abilities, abdominal pain, nausea, and constipation.(1)

DISCUSSION: Concurrent administration of a single dose (600 mg) of cyclosporine, an OATP1B1 inhibitor, increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of eluxadoline (100 mg) by 4.4-fold and 6.2-fold, respectively.(1) OATP1B1 inhibitors include: atazanavir, belumosudil, boceprevir, cyclosporine, darunavir, encorafenib, eltrombopag, erythromycin, gemfibrozil, leflunomide, leniolisib, letermovir, lopinavir, paritaprevir, resmetirom, rifampin, ritonavir, roxadustat, saquinavir, simeprevir, telaprevir, teriflunomide, tipranavir, vadadustat, and voclosporin.(1,2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Agents With Hyponatremia Risk/Desmopressin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Carbamazepine, chlorpromazine, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants increase the risk of hyponatremia.(1-3)

CLINICAL EFFECTS: Concurrent use may increase the risk of hyponatremia with desmopressin.(1-3)

PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (glucocorticoids, loop diuretics).

PATIENT MANAGEMENT: The concurrent use of agents with a risk of hyponatremia with desmopressin may increase the risk of hyponatremia. If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83 mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1)

DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4)

Eluxadoline is contraindicated in patients who do not have a gallbladder because of the increased risk for pancreatitis and/or sphincter of Oddi spasm in such patients; the drug also is contraindicated in patients with known or suspected biliary duct obstruction or sphincter of Oddi disease or dysfunction because of the increased risk for sphincter of Oddi spasm. (See Pancreatitis and also see Sphincter of Oddi Spasm under Cautions: Warnings/Precautions.)

Because of the increased risk of acute pancreatitis, eluxadoline is contraindicated in patients with alcoholism, alcohol abuse or addiction, alcohol consumption in excess of 3 alcoholic beverages per day, or a history of pancreatitis or structural pancreatic diseases, including known or suspected pancreatic duct obstruction. (See Pancreatitis under Cautions: Warnings/Precautions.)

Eluxadoline is contraindicated in patients with severe hepatic impairment (Child-Pugh class C) because of the potential for substantially increased plasma concentrations of the drug. (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

Eluxadoline also is contraindicated in patients with a history of chronic or severe constipation or sequelae from constipation and those with known or suspected mechanical GI obstruction, since these patients may be at risk for severe complications of bowel obstruction.

• Alcohol use disorder
• Biliary obstruction
• Biliary tract disorder
• Child-pugh class C hepatic impairment
• Congenital absence of gallbladder
• Gastrointestinal obstruction
• History of cholecystectomy
• Pancreatitis

• Child-pugh class A hepatic impairment
• Child-pugh class B hepatic impairment
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Disease of liver
• Severe constipation

There are no moderate contraindications for this drug.

Adverse effects reported in more than 2% of patients receiving eluxadoline 75 or 100 mg twice daily for irritable bowel syndrome (IBS) with diarrhea (and with greater frequency than in patients receiving placebo) include constipation, nausea, abdominal pain, upper respiratory tract infection, vomiting, nasopharyngitis, abdominal distention, bronchitis, dizziness, flatulence, rash, increased ALT concentrations, fatigue, and viral gastroenteritis.

Less Frequent

• Abnormal hepatic function tests
• Increased alanine transaminase

Rare or Very Rare

• Accidental fall
• Acute respiratory failure
• Anaphylaxis
• Angioedema
• Bronchospastic pulmonary disease
• Dyspnea
• Fecal impaction
• Gastrointestinal obstruction
• Increased aspartate transaminase
• Intestinal perforation
• Pancreatitis
• Spasm of sphincter of oddi
• Throat constriction

More Frequent

• Acute abdominal pain
• Constipation
• Nausea

Less Frequent

• Abdominal distension
• Bronchitis
• Dizziness
• Fatigue
• Flatulence
• Pharyngitis
• Pruritus of skin
• Skin rash
• Upper respiratory infection
• Viral gastroenteritis
• Vomiting

Rare or Very Rare

• Asthma
• Chest pain
• Chest tightness
• Drowsy
• Euphoria
• Gastroesophageal reflux disease
• Sedation
• Wheezing

No enhanced messaging available.

Safety and efficacy of eluxadoline have not been established in pediatric patients.

There are no studies in pregnant women assessing eluxadoline-associated risks. Reproduction studies in rats and rabbits have not revealed evidence of teratogenicity, and a prenatal and postnatal development study in rats revealed no evidence of adverse effects in the offspring.

It is not known whether eluxadoline is distributed into human milk; however, the drug is distributed into milk in rats. The benefits of breast-feeding and the importance of eluxadoline to the woman should be considered along with any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.

In clinical studies evaluating eluxadoline in patients with IBS, 7.7% of those who received the study drug were 65 years of age or older, while 0.8% were 75 years of age or older. No overall differences in efficacy or types of adverse effects were observed between geriatric patients and younger adults. However, a higher proportion of geriatric patients, compared with younger adults, experienced adverse effects (66 versus 59%), serious adverse effects (9 versus 4%), and adverse GI effects (39 versus 28%).